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Identification of rat faecal metabolites of ebastine by B/E linked scanning liquid secondary ion mass spectrometry
Author(s) -
Yoshida K.,
Hatoyama T.,
Fujii T.,
Kagemoto A.,
Miyazaki H.,
Naruto S.
Publication year - 1994
Publication title -
biological mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1052-9306
DOI - 10.1002/bms.1200230702
Subject(s) - chemistry , hydroxylation , chromatography , moiety , mass spectrometry , metabolism , hydroxymethyl , stereochemistry , organic chemistry , biochemistry , enzyme
The identification of rat faecal metabolites of a new antihistaminic agent, ebastine, 4′‐ tert ‐butyl‐4‐[4‐(diphenylmethoxy)piperidino]butyrophenone, is presented. After oral administration of ( 14 C)ebastine (20 mg kg −1 ) to rats, 84% of the radioactive dose was excreted in the 24 h faeces. Unchanged drug and five metabolites were isolated from the faeces by thin‐layer chromatography and solid‐phase extraction, and their structures were identified by liquid secondary ion mass spectrometry using the B/E linked scanning technique. The main metabolic pathways were oxidation of a terminal methyl group to give the hydroxymethyl and carboxyl derivatives, and hydroxylation of a phenyl ring in the diphenylmethoxy moiety. In addition to the oxidative mechanism, metabolism of ebastine involved sulphate conjugation. It is noteworthy that M‐4, having both phenolic and alcoholic hydroxyl groups, was sulphated selectively in the latter position.